Topiramate for the treatment of epilepsy and other nervous system disorders

Abstract

Initially synthesized as an oral hypoglycemic agent, topiramate was approved for use as an anticonvulsant in 1996. Its broad spectrum efficacy in epilepsy, including as monotherapy and in children, is well established. Topiramate has also been used in the management of nonepileptic neurologic and psychiatric conditions, including migraine prophylaxis (with firmly established efficacy), obesity (with some evidence of long-term maintenance of weight loss), substance dependence, bipolar disorder and neuropathic pain, and it has been investigated as a possible neuroprotective agent. Paresthesias and cognitive side effects are the most common troublesome adverse effects. Recent trends towards lower doses may help achieve the best combination of efficacy and tolerability.

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations

“…As observed for sulphonamides, also sulphamates and sulphamides exert their inhibitory action through coordination to zinc ion and consequent substitution of the water molecule/ hydroxide ion 1 . Plenty of studies has been reported showing that many sulphamates possess effective inhibitory properties against all known human isoforms 1,11,[16][17][18][19] , with some derivatives, such as the sugar sulphamate topiramate (compound 1 in Figure 1), successfully used for the treatment of a variety of diseases such as epilepsy, migraine, and obesity 20,21 . Although the sulphamide group was initially considered not particularly suitable for obtaining potent CAIs 22 , several compounds containing a primary sulphamide moiety have also been proved to possess a high CA inhibition activity 1,11,19,23 .…”

Topiramate versus Carbamazepine for the Treatment of Classical Trigeminal Neuralgia

“…[12] It is used to treat CNS conditions such as neuropathies, eating disorders, alcohol and drug dependence, migraine, nerve injury, restless leg syndrome, essential tremor and psychiatric diseases. [13][14][15] Topiramate is generally well tolerated at low doses [16] but at high doses it may cause various kinds of adverse effects including paraesthesia, dysphasia, fatigue, confusion and insomnia. [17] Topiramate is also used for the treatment of classical trigeminal neuralgia, but its efficacy remains controversial.…”

Standalone Drugs

“…Structurally, it bears no resemblance to previously used anticonvulsant agents and was originally synthesized as a chemical intermediate during a program to identify inhibitors of fructose-1,6-bisphosphatase as potential antidiabetic agents [87,88]. In combination with the sulfamate functionality, which appears to be essential for activity, many variations on the scaffold are tolerated.…”